Alcohol dependence is a significant and prevalent public health problem affecting approximately 4 percent of the U.S. adult population. Individuals with alcohol dependence actively seek treatment annually, and long-term alcohol abstinence varies from 40 to 60 percent. Because of the high smoking prevalence and trends toward heavier smoking, alcoholic smokers are at high risk for both morbidity and mortality related to alcohol consumption and tobacco dependence. Although several studies have evaluated pharmacotherapy for tobacco dependence in recovering alcoholic smokers, few have evaluated pharmacotherapy for tobacco dependence among currently drinking alcoholic smokers. Varenicline is the most effective medication currently available for treating tobacco dependence. While some randomized trials have included recovering alcoholics, active alcoholism has been an exclusion criterion for these trials. Thus, this proposal would be for the first such clinical trial in currently drinking alcoholic smokers. In addition to helping smokers to stop smoking, varenicline has also been shown to reduce alcohol consumption in rats. The goal of this application is to explore the potential efficacy of varenicline for treating tobacco dependence and reducing drinking among alcohol dependent smokers. The investigators hypothesize that 12 weeks of treatment with varenicline, a partial nicotinic acetylcholine receptor agonist will be more effective than placebo in treating tobacco dependence and reducing nicotine withdrawal symptoms in currently drinking alcoholic smokers. The investigators will also explore whether varenicline has an effect on drinking behavior among currently drinking alcoholics. The investigators propose the following specific aims to test these hypotheses in 70 currently drinking alcoholic smokers recruited at the Mayo Clinic in Rochester, Minnesota: Primary: 1) To assess the efficacy of varenicline 1.0 mg twice daily for 12 weeks versus placebo for increasing 7-day point prevalence and prolonged smoking abstinence at the end-of-treatment among currently drinking alcoholic smokers. 2) To evaluate the efficacy of varenicline 1.0 mg twice daily versus placebo in reducing nicotine withdrawal symptoms in currently drinking alcoholic smokers who are trying to stop smoking. Secondary: 3) To assess the efficacy of varenicline 1.0 mg twice daily for 12 weeks versus placebo for reducing the number of heavy drinking days (e5 standard alcohol drinks for men and e4 standard alcohol drinks for women per day) per month in currently drinking alcoholic smokers. PUBLIC HEALTH RELEVANCE: Smoking is a serious problem in alcoholics as approximately 50 percent of patients previously treated for alcoholism or other drug dependence die from a tobacco-caused disease such as lung cancer, emphysema and heart disease. There is a sizable literature on treating recovering alcoholic smokers, but very little on treating actively drinking alcoholic smokers. Thus, the investigators are proposing a research study to see if a new medication, varenicline (Chantix(R)), will prove effective in helping currently drinking alcoholic cigarette smokers to stop smoking and relieve their nicotine withdrawal symptoms. The investigators will explore whether varenicline might also have an effect on drinking behavior in this group. If successful, this will be an important step forward in treating alcoholic smokers and will result in lives saved by reducing tobacco-caused deaths in this high risk population.